Exploration in the mechanism of rhubarb for the treatment of hyperviscosity syndrome based on network pharmacology

• Published in: Journal of ethnopharmacology Vol. 261; p. 113078
• Main Authors: Gao, Dan, Wu, Shan-na, Zhang, Cong-en, Li, Rui-sheng, Liu, Zhen-jie, Xiao, Xiao-he, Li, Lin, Wang, Jia-bo, Zhang, Lan, Niu, Ming
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 28.10.2020
• Subjects: Animals; Aspirin - pharmacology; Blood Platelets - drug effects; Blood Platelets - metabolism; Blood Viscosity - drug effects; Disease Models, Animal; Fibrinogen - metabolism; Hematologic Diseases - blood; Hematologic Diseases - drug therapy; Hematologic Diseases - pathology; Hyperviscosity syndrome; Male; Network pharmacology; Plant Extracts - isolation & purification; Plant Extracts - pharmacology; Platelet activation; Platelet Aggregation - drug effects; Platelet Aggregation Inhibitors - isolation & purification; Platelet Aggregation Inhibitors - pharmacology; Promoting blood circulation to remove blood stasis; Prothrombin - metabolism; Rats, Sprague-Dawley; Rheum - chemistry; Rhubarb; Signal Transduction; Syndrome; Systems Biology; P-sel; Phy; Platelet activation; HVS; PV; Emo; PBRB; FGG; WBV; F2; QC; Hyperviscosity syndrome; TXB2; Network pharmacology; Rhubarb; Promoting blood circulation to remove blood stasis; HMD; TCM
• ISSN: 0378-8741; 1872-7573
• DOI: 10.1016/j.jep.2020.113078

Hyperviscosity syndrome (HVS) is a major risk factor for thrombotic diseases. Rhubarb, well-known as a traditional Chinese medicine, exhibits multiple pharmacological activities, especially for promoting blood circulation to remove blood stasis (PBRB), which has been become a functional health food for decreasing the risk of cardiovascular diseases. However, due to the complexity of rhubarb components, it is still difficult to clarify the specific targets of effective substances in PBRB, and the pharmacodynamic mechanism needs to be further probed. The “compound-target-cell-disease” network analysis was initially used to predict potential targets and bioactive compounds. The effect of rhubarb for the treatment of HVS was examined by histopathology and biochemical assays based on the HVS rat model. Through the “compound-target-cell-disease” network analysis, eight potential therapeutic targets were eventually screened out, and platelets were predicted as the main effector cells of rhubarb in PBRB. Among targets coagulation factor II (prothrombin, F2) and fibrinogen gamma chain (FGG) were closely related to platelets, and five compounds associated with F2 and FGG were predicted including emodin-8-O-beta-D-glucopyranoside (Emo), physcion-8-O-beta-D-glucopyranoside (Phy), procyanidin B-5,3′-O-gallate, torachrysone-8-O-beta-D-(6′-oxayl)-glucoside and epicatechin. Furthermore, thoracic aorta histopathology and biochemical examinations showed middle dose of rhubarb (0.42 g/kg/day) significantly ameliorated pathological changes, hemorheology parameters, as well as levels of representative biomarkers such as plasma P-selectin (P-sel) and thromboxane (TXB2) in platelet activation compared to HVS rat model, whose effects were comparable to the positive drug aspirin or even better. Finally, it was further validated F2 and FGG as the major effective targets of rhubarb as well as its two active ingredients Emo and Phy in PBRB. This study may provide an innovative way and scientific information to further understand the main effective components of rhubarb and its mechanisms about targets of F2 and FGG in PBRB, especially the new therapeutic target FGG, which also provide a basis for establishing a quality control for rhubarb by bioassays that could correlate the clinical efficacy and its mechanism. [Display omitted] •The “compound-target-cell-disease” network analysis is initially used.•Only middle dose of rhubarb appears to significantly ameliorated HVS.•FGG was first reported as a target for drug on the effect of PBRB.